From http://publica.fraunhofer.de/documents/N-141596.html it is known that polycarbonate-urethanes are used in medical technology because of their bio- and hemocompatibility, biostability, toughness and gliding properties in highly stressed implants. A high degree of ability to modify the surface allows the application of antimicrobial or antithrombogenic coatings.
Trzaskowski M., et al., The Challenges of Modern Technology 2 (1), 2011, pages 19 to 22 discloses a polyvinylpyrrolidone hydrogel coating on a surface of polyurethane for an artificial heart implant. Polyvinylpyrrolidone is a highly hydrophilic polymer that forms hydrogels in water. It is expected to increase the biocompatibility of the coated material and prevent blood from clotting on the surface of the PUR. Furthermore, it is disclosed that previously hemocompatibility has been improved by coating of PUR surfaces with proteins that actively prevent blood from coagulation, e.g. heparin, urokinase or thrombomodulin. Insufficient durability of these modifications is mentioned as their main disadvantage.
Sask, K. N., et al., Langmuir 2012, 28, pages 2099 to 2106 discloses the modification of polyurethane surface with an antithrombin-heparin complex for blood contact. It is described to use isocyanate chemistry for covalent coupling of polyethylene oxide (PEO) to the surface of the polyurethane. Subsequently the antithrombin-heparin complex is covalently coupled to the PEO.
A covalent coating of polyurethane catheters with an antithrombin-heparin complex via PEO is known from Du, Y. J., et al., Journal of Biomedical Materials Research Part A, Volume 80 A, Issue 1, 2007, pages 216 to 225.
From U.S. Pat. No. 6,491,965 B1 a medical device comprising glycosaminoglycan-antithrombin III/heparin cofactor II conjugates is known. The conjugates are covalently attached to a polymer of the device. The polymer may be polyurethane or polycarbonate-polyurethane. The device may be a cardiac catheter, a cardiopulmonary bypass circuit, a dialysis circuit or an in vivo prosthesis.
WO 2011/147409 describes a coating of endoprostheses with a coating consisting of a tight mesh of polymer fibres. The polymer may be polyurethane. The endoprostheses may comprise an anti-restenotic active substance such as an antithromboticum, e. g. antithrombin. The active substance may be contained in the mesh of polymer fibres in covalently, adhesively or ionically bound form.
From WO 03/034944 A1 a coating of stents for preventing restenosis is known. The coating may contain an antithrombotic active substance such as antithrombin. The stent is covered with a first hemocompatible coating and at least one second coating comprising the active substance. The hemocompatible coating may consist of heparin, oligo- and polysaccharides, polyacrylic acid, polyvinylpyrrolidone and other polymers.
From the doctoral thesis “Oberflächenmodifizierung von Polyvinylidenfluorid zur Minimierung der Proteinadsorption”, Ademovic Zahida, 2002, Institute of Technology Aachen it is known to bind polyacrylic acid to the surface of PVDF and to bind polyethyleneimine (PEI) to the carboxy groups of the polyacrylic acid via the use of carbodiimide. Subsequently polyethylene glycol aldehydes, carboxymethylated dextran or carboxymethylated hydroxyethyl starch were covalently coupled to the amino groups of PEI. The aim of this coating was to generate a surface coating that reduces or prevents non-specific protein binding and the resulting cell adhesion. Coating with polyacrylic acid requires a long-term incubation at about 90° C. This may result in a change of the properties of the coated substrate. A lower temperature results in an ineffective coating.
From U.S. Pat. No. 4,521,564 an antithrombogenic polyurethane polymer is known. The polymer comprises a polyurethane substrate, a polymeric amine covalently bonded to said polyurethane substrate and an antithrombogenic agent covalently bonded to said polymeric amine. The polymeric amine may be polyethyleneimine.
From U.S. Pat. No. 5,132,108 a medical device having a biocompatible polymeric surface is known. Said biocompatible polymeric surface comprises a surface which has been modified by subjecting the polymeric surface to radiofrequency discharge treatment within a plasma medium having between about 40 and about 90 volume percent water vapor, the balance of that plasma medium being between about 10 and about 60 volume percent oxygen based upon the total volume of plasma medium. The plasma treatment is followed by treatment with a coupling agent and a spacer component having amine groups forming covalent linkages with the polymeric surfaces which had been subjected to radiofrequency discharge treatment with said plasma medium, and then by treatment with an antithrombogenic, fibrinolytic or thrombolytic agent having acid functionality contacting and covalently bonding with the spacer component-treated polymeric surface. The polymeric surface may be a polyurethane surface. The spacer molecule which provides reactive sites for attachment of the antithrombogenic agent may be polyethyleneimine. Covalent linkages between the reactive sites on the polymeric surface and the amine groups of the spacer molecule may be provided by using a suitable coupling agent such as 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC) or dicyclohexyl carbodiimide (DCC). The plasma medium is provided within a chamber. Air or other gas is first evacuated from the radiofrequency treatment chamber until virtually no air or other gas remains therewithin. Then the water vapor is pumped or otherwise injected into the chamber and a radio frequency electric field is generated within the reactor chamber, thereby inducing treatment of the polymeric surface.